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권형주(Hyeong Ju Kwon),강경훈(Gyeong Hoon Kang) 대한의학유전학회 2009 대한의학유전학회지 Vol.6 No.1
프로모터 CpG island 과메틸화와 히스톤 변경으로 대변되는 후성유전적 변화는 거의 모든 종류의 암에서 발견되는 중요한 발암기전이다. 인간유전자의 60-70% 가량이 프로모터에 CpG islands를 가지고 있으며, 이 유전자들 중 일부가 과메틸화됨으로써 해당유전자의 발현이 차단되고, 종양억제기능이 소실되어 종양세포의 성장을 촉진하게 된다. 암에는 프로모터 CpG island 과메틸화라는 국소적 변화 이외에, 유전체 전반에 걸친 탈메틸화를 동시에 보이는 경우가 대부분인데, 이러한 유전체 저메틸화는 염색체 불안정성과 밀접한 연관관계가 있다. 국소적 과메틸화와 전반적인 저메틸화라는 이러한 상반된 DNA 메틸화 변화는 암세포뿐만 아니라 그 전단계 병변인 이 형성 병변에서도 관찰된다. 프로모터 CpG island 과메틸화는 유전자 발현억제 기전으로서의 중요성뿐만 아니라 종양표지자로서의 중요성이 부각되고 있다. 즉, 정상세포에서는 관찰되지 않으면서 암세포에서만 관찰되는 프로모터 CpG island 과메틸화는 암세포의 바이오마커로서의 가치가 있으며, 이를 이용하여 체액에서 암을 진단하려는 시도들이 이루어지고, 이를 활용한 암의 분자진단방법이 개발되고 있다. 또한 이러한 DNA 메틸화는 암환자의 예후 판정이나 항암치료제의 감수성 결정 등에 활용되고 있다. 본 원고에서는 인체 암세포에서의 DNA 메틸화 변화에 관하여 소개하고자 한다. Epigenetic changes represented by promoter CpG island hypermethylation and histone modification are an important carcinogenetic mechanism, which is found in virtually all histologic types of human cancer. About 60-70% of human genes harbor CpG islands in their promoters and 5’ exonal sequences, and some of them undergo aberrant promoter CpG island hypermethylation and subsequent downregulation of gene expression. The loss of expression in tumor suppressor or tumor-related genes results in acceleration of tumorigenic processes. In addition to regional CpG island hypermethylation, diffuse genomic hypomethylation represents an important aspect of DNA methylation changes occurring in human cancer cells and contributes to chromosomal instability. These apparently contrasting methylation changes occur not only in human cancer cells, but also in premalignant cells. CpG island hypermethylation has gained attention for not only the tumorigenic mechanistic process, but also its potential utilization as a tumor biomarker. DNA methylation markers are actively investigated for their potential uses as tumor biomarkers for diagnosis of tumors in body fluids, prognostication of cancer patients, or prediction of chemotherapeutic drug response. In this review, these aspects will be discussed in detail.
BRAF(V600E) 돌연변이 갑상선 역형성암에서 BRAF(V600E) 억제에 의한 EGFR 발현 증가가 표적치료에 대한 저항성발현과 상피-간질세포이행과정에 미치는 영향분석
변형권(Hyung Kwon Byeon),나휘정(Hwi Jung Na),양연주(Yeon Ju Yang),박재홍(Jae Hong Park),권형주(Hyeong Ju Kwon),장재원(Jae Won Chang),반명진(Myung Jin Ban),김원식(Won Shik Kim),신동엽(Dong Yeob Shin),이은직(Eun Jig Lee),고윤우(Yoon Wo 대한두경부종양학회 2014 대한두경부 종양학회지 Vol.30 No.2
Background and Objectives:Anaplastic thyroid carcinoma(ATC) is a rare but highly aggressive thyroid ma-lignancy that is associated with an extremely poor survival despite the best multidisciplinary care. BRAF(V600E) mutation is detected in about a quarter of ATC, but unlike its high treatment response to selective BRAF inhibitor (PLX4032) in metastatic melanoma, the treatment response of ATC is reported to be low. The purpose of this study is to investigate the innate resistance mechanism responsible for this low treatment response to BRAF inhibitor and its effect on epithelial-mesenchymal transition(EMT). Materials and Methods:Two ATP cell lines, 8505C and FRO were selected and treated with PLX4032 and its drug sensitivity and effects on cell migration and EMT were examined and compared. Further investigation on the changes in signals responsible for the different treatment response to PLX4032 was carried out and the same ex-periment was performed on both orthotopic and ectopic xenograft mouse models. Results:FRO cell line was more sensitive to PLX4032 treatment compared to 8505C cell line. The resistance to BRAF inhibition in 8505C was due to increased expression of EGFR. Effective inhibition of both EGFR and p-AKT was achieved after dual treatment with BRAF inhibitor(PLX4032) and EGFR inhibitor(Erlotinib). Similar results were confirmed on in vivo study. Conclusion:EGFR-mediated reactivation of the PI3K/AKT pathway and MAPK pathway contributes to the relative insensitivity of BRAF(V600E) mutant ATC cells to PLX4032. Dual inhibition of BRAF and EGFR leads to sustained treatment response including cell invasiveness.
혈액검사에서 정상이었으나 당뇨망막병증과 당뇨신병증 소견을 보여 당뇨로 진단된 1예
김재혁(Jae Hyuk Kim),권형주(Hyeong Ju Kwon),김선웅(Sun Woong Kim) 대한검안학회 2018 Annals of optometry and contact lens Vol.17 No.1
Purpose: To report a case of diabetic mellitus following diabetic retinopathy and diabetic nephropathy in a patient with no history of previous diabetes mellitus and no evidence of diabetes in the blood test. Case summary: A 39-year-old man with no previous history of diabetes mellitus was referred to our clinic for further diagnosis because of suspected diabetic nephropathy. No specific findings on the anterior segment were found on slit lamp microscopy. Fundus examination revealed flame-shaped retinal hemorrhages and cotton wool spots around optic disc and macula in both eyes. No other specific findings were observed. Urine glucose was not detected in the urine test at admission and glucose was normal in the blood test. The hemoglobin A1c (HbA1c) test was normal in 5.8. Diabetic retinopathy was diagnosed by fundus examination, and diabetes was confirmed by oral glucose tolerance test (OGTT test). Conclusions: Although the patient was not aware of the presence of diabetes, diabetic retinopathy was often diagnosed by fundus examination. In this case, diabetic retinopathy was diagnosed by fundus examination after suspicion of diabetes through renal biopsy in the absence of diagnosis of diabetes in internal medicine. After all, diabetes could be diagnosed in internal medicine conversely. It can be reemphasized once again how important it is to perform fundus examination early in diagnosing diabetic patients.
이달의 X-선 : 척추 경막외 기종이 동반된 기관지 천식 1례
이철호 ( Lee Cheol Ho ),권형주 ( Kwon Hyeong Ju ),박영우 ( Park Yeong U ),이무열 ( Lee Mu Yeol ),유흥선 ( Yu Heung Seon ),황인석 ( Hwang In Seog ),김진관 ( Kim Jin Gwan ),김미영 ( Kim Mi Yeong ),신미정 ( Sin Mi Jeong ),황순철 ( Hw 대한결핵 및 호흡기학회 2000 Tuberculosis and Respiratory Diseases Vol.49 No.3
한성민(Sung Min Han),박상만(Sang Man Park),권형주(Hyeong Ju Kwon),김지훈(Ji Hoon Kim) 대한두경부종양학회 2017 대한두경부 종양학회지 Vol.33 No.2
Mammary analogue secretory carcinoma (MASC) is a rare malignant tumor of the salivary gland, which was first described in 2010. 1) In this case report, we describe a 62-year-old woman with a MASC of the parotid gland, who initially presented with an asymptomatic preauricular mass. At first, computed tomography (CT) and fine needle aspiration cytology were performed; these suggested a possible Warthin’s tumor but also some suspicious malignant findings. For the main treatment, adequate parotidectomy was conducted via modified Blair incision to remove the tumor. Postoperative pathology report revealed a MASC of the parotid gland. Specific MASC findings were observed upon immunohistochemical examination.